The benzodiazepine compounds have been widely used as antianxietic agents. Though these compounds have potent anxiolytic action, they have side effects such as muscle-relaxation effect, sedative action, drug dependence and so on. Therefore, there are some problems that these agents must be cautiously applied to patients suffering from anxiety neurosis like psychosomatic disease in the daytime (usually called as daytime anxiety). Recently, the researches for compounds having non-benzodiazepine structure have been devoted to the development of antianxietic drugs which act selectively on anxiety. The representative of such compounds is buspirone (INN). Differing from hitherto benzodiazepine compounds, buspirone is known not to bind to benzodiazepine receptor but has high affinity for serotonin 1A receptor and exhibits antianxietic action by an interaction with serotonin 1A receptor. Since such new compounds have superior property such as high safety, less habit-forming and less probability of abuse, they are expected to be new prototype of antianxietic drugs. However, the problems to be solved still remain since they need long time to exhibit their activities and have side effects in extrapyramidal system.
The existing antipsychotic drugs are effective on so called positive symptoms like hallucination, delusion or the like as well as on psychomotor excitement but not effective on negative symptoms like apathy, abulia, disorder of cognition and so on. Further, as unavoidable side effects such as acute dystonia, akathisia or Parkinsonism are observed at the initial stage of treatment with antipsychotic drugs and extrapyramidal syndromes like late dyskinesia are observed during the long term administration. Because of the limitation of the treatment with the existing antipsychotic drugs, the development of antipsychotic drugs which are effective on negative symptoms and with reduced side effects has been expected. From this point of view, it is desired to develop new antipsychotic drugs which have affinity for both serotonin and dopamine receptors, and especially bind more selectively to serotonin receptor.
Recently a relationship between serotonin 1A receptor and hypotensive action has been reported. That is, it is known that 8-hydroxy-2-dipropylaminotetralin (8OH-DPAT) which has high affinity for serotonin 1A receptor lowers blood pressure through serotonin 1A receptor of medulla oblongata. In accordance with this fact, the compounds having high affinity for serotonin 1A receptor can be developed as antihypertensive drug. This kind of compounds are expected to be useful antihypertensive drug because they do not cause rebound phenomenon, hyposalivaton or sympatheticotonia (that is, bradycardic action rather than tachcardiac action). For example, it is known that piperazine derivatives are one of such drugs exhibiting hypotensive action by central action mechanism (U.S. Pat. No. 4,833,142).